Aβ-Amyloid Lowering with Monoclonal Antibodies for Alzheimer's Disease: Appropriate Use Recommendations for Australasian Conditions

Introduction::The advent of potentially disease-modifying therapies for Alzheimer's disease (AD) using monoclonal antibodies targeting Aβ-amyloid (Aβ) presents many opportunities and challenges. Identification of patients who might have the most benefit is the highest priority, where the current data suggest that intervention at the mild (prodromal) and early clinical dementia stages of AD at highest tolerated dosage provides the best results. Managing side effects [amyloid-related imaging abnormalities (ARIA) – edema (E) and hemorrhage (H)] requires rigorous inclusion and exclusion criteria and close monitoring, particularly in the first 12 months of therapy. Main recommendations: Regulatory prescriptive advice and academic expert recommendations for the US have been published. Australasian regulatory guidelines are likely to be consistent with those from the FDA. While the decision to start therapy may be relatively straightforward, determining the criteria for dose reduction or cessation may be problematic. This will be addressed in the near future with experience coming from treatment strategies based on "real world" experience. Post-marketing surveillance of the use of this class of therapy, using Clinical Quality Registries, will provide the supportive evidence on safety and effectiveness. Changes in management as a result of these recommendations: This new class of immunotherapies will require careful monitoring for safety and effectiveness which will alter current diagnostic and therapeutic service delivery models for persons presenting with mild (prodromal) and early stages of AD and related conditions. Use of imaging and biofluid biomarkers will become mandatory for determining eligibility for starting, reducing and ceasing these immunotherapies.